蛇床子素药理活性的研究概况

概述近10年国内外对中药提取物蛇床子素（osthole）免疫增强活性、抗肿瘤活性、抗肝炎活性、抗骨质疏松及其他多种药理活性的研究。目前蛇床子素还未成为药物推向市场，但其可开发成为肿瘤防治用药，作为治疗和控制肝病及抗骨质疏松药物的前景也十分广阔。     

蛇床子素对小鼠实验性肝损伤的保护作用

目的:探讨蛇床子素对小鼠CCl4肝损伤的保护作用。方法:采用CCl4小鼠急性肝损伤模型,测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)活性、肝组织MDA含量,并观察肝组织病理变化。结果:蛇床子素能保护CCl4所致小鼠肝损伤,表现为血清ALT、AST活力和肝脏MDA含量下降,同时其肝脏病变较模型组为轻。结论:蛇床子素对CCl4所致小鼠肝损伤具有保护作用。     

RP-HPLC法同时测定蛇床子中蛇床子素、欧芹属素乙和异茴芹素的含量

目的建立蛇床子Cnidiummonnieri中蛇床子素(osthole)、欧芹属素乙(imperatorin)和异茴芹素(isopimpinellin)的高效液相色谱测定方法。方法采用VercoparkInertsilN-5ODS柱,1%醋酸-甲醇(梯度为0～30min1%醋酸95%～5%)为流动相,检测波长254nm。结果该法回收率蛇床子素为99.1%,欧芹属素乙为95.8%,异茴芹素为97.3%;RSD蛇床子素为1.8%,欧芹属素乙为0.8%,异茴芹素为3.3%(n=5)。结论本方法为蛇床子药材、蛇床子提取物及含蛇床子药材的复方的质量评估提供了可靠的依据。     

HPLC测定妇康胶囊中蛇床子素的含量

目的：建立妇康胶囊中蛇床子素的含量测定方法。方法：色谱柱为Reliasil C18（250×4.6 mm,5μm）,流动相为乙腈-水（67∶33）,检测波长321nm,流速为1.0 ml/min,柱温为40℃。结果：蛇床子素在9.26-45.65μg/ml范围间呈良好的线性关系,r=0.9996（n=5）,平均回收率为100.13%,RSD为2.33%（n=9）。结论：高效液相色谱法（HPLC）简便可行、重复性好,可用于妇康胶囊中有效成分蛇床子素的含量测定。     

Osthole or imperatorin‐mediated facilitation of glutamate release is associated with a synaptic vesicle mobilization in rat hippocampal glutamatergic nerve endings

Osthole and imperatorin, two active compounds of Cnidium monnieri (L.) Cusson, have previously been shown to facilitate depolarization‐evoked glutamate release from rat hippocampal nerve terminals by increasing voltage‐dependent Ca²⁺ entry. In this study, we further investigated whether osthole and imperatorin possess an action at the exocytotic machinery itself, downstream of a Ca²⁺ influx. Our data showed that ionomycin‐induced glutamate release and KCl‐evoked FM1‐43 release were facilitated by osthole and imperatorin, suggesting that some steps after Ca²⁺ entry are regulated by these two compounds. Consistent with this, osthole or imperatorin‐mediated facilitation of ionomycin‐induced glutamate release was occluded by cytochalasin D that inhibits actin polymerization, implying that the disassembly of cytoskeleton is involved. In addition, the facilitatory action of osthole or imperatorin on ionomycin‐induced glutamate release was attenuated by the Ca²⁺/calmodulin‐dependent kinase II (CaMKII) inhibitor KN62. Furthermore, Western blotting analysis further showed that osthole or imperatorin significantly increased ionomycin‐induced phosphorylation of CaMKII and synapsin I, the main presynaptic target of CaMKII. These results suggest, therefore, that osthole or imperatorin‐mediated facilitation of glutamate release involves modulation of downstream events controlling synaptic vesicle recruitment and exocytosis, possibly through an increase of CaMKII activation and synapsin I phosphorylation, thereby increasing synaptic vesicle availability for exocytosis. Synapse 64:390–396, 2010. © 2009 Wiley‐Liss, Inc.     

N-脂肪酰-N-三甲基壳聚糖的合成及其对蛇床子素的增溶作用

目的 合成2类两亲性壳聚糖（chitosan,CS）衍生物,自组装成聚合物胶束作为难溶性药物的新型递药载体。方法 先将CS与碘甲烷反应生成N-三甲基壳聚糖（trimethyl chitosan,TMC）,然后在TMC的氨基上引入长链脂肪酸（软脂酸和癸酸）,合成了两亲性的N-脂肪酰-N-三甲基壳聚糖（N-fatty acyl-N-Trimethyl chitosan,FA-TMC）衍生物。通过FT-IR、¹H-NMR和元素分析法,对衍生物的分子结构和N-位取代度进行表征,同时以疏水性药物蛇床子素（osthole,OST）为模型,探讨其胶束增溶特性。结果 实验合成了2类6种不同的新型CS衍生物,分析显示季胺化程度和脂肪酰基接枝率对FA-TMC的胶束性质有较大的影响;对于超声法制备的OST载药胶束,季胺化程度为62.00%、软脂酰基接枝率为13.37%的N-软脂酰-N-三甲基壳聚糖（N-palmitoyl-N-trimethyl chitosan,PA-TMC）和季胺化程度为43.06%、癸酰基接枝率为22.00%的N-癸酰-N-三甲基壳聚糖（N-caprinoyl-N-trimethyl chitosan,CA-TMC）的包封率分别为76.67%、79.11%,载药量分别为19.01%、19.08%,可使OST在水中的溶解度提高两个数量级。结论 FA-TMC是一种具有潜在应用价值的增溶载体,其在水中能自组装形成胶束,并对OST有明显的增溶作用,为OST制剂深入研究与应用奠定了基础。     

治疗牙周炎所致牙槽骨吸收的前景药物

牙周炎是成人牙齿丧失的首要原因,以牙周组织的炎症和牙槽骨的吸收为主要临床表现。现今治疗牙周炎的药物主要是硝基咪唑类、青霉素类和四环素类,用于控制菌斑、消除炎症;但缺乏能够改建牙槽骨、促进牙槽骨再生的药物,因此影响了临床疗效。寻找促进成骨的药物尤为重要,通过查阅文献,很多研究表明辛伐他汀、贝尼地平、柚皮苷和蛇床子素具有成骨作用,能够修复牙槽骨缺失,并可制成多种缓控释剂型,可提高药效并避免全身用药引起的不良反应。联合抗菌药物与成骨药物制成缓控释制剂并采用局部用药的方式为牙周炎的治疗提供了新的治疗策略。     

Osthole inhibits proliferation of human breast cancer cells by inducing cell cycle arrest and apoptosis

Recent studies have revealed that osthole,an active constituent isolated from the fruit of Cnidium monnieri(L.) Cusson,a traditional Chinese medicine,possesses anticancer activity.However,its effect on breast cancer cells so far has not been elucidated clearly.In the present study,we evaluated the effects of osthole on the proliferation,cell cycle and apoptosis of human breast cancer cells MDA-MB 435.We demonstrated that osthole is effective in inhibiting the proliferation of MDA-MB 435 cells,The mitochondrion-mediated apoptotic pathway was involved in apoptosis induced by osthole,as indicated by activation of caspase-9 and caspase-3 followed by PARP degradation.The mechanism underlying its effect on the induction of G1 phase arrest was due to the up-regulation of p53 and p21 and down-regulation of Cdk2 and cyclin D1 expression.Were observed taken together,these findings suggest that the anticancer efficacy of osthole is mediated via induction of cell cycle arrest and apoptosis in human breast cancer cells and osthole may be a potential chemotherapeutic agent against human breast cancer.     

蛇床子素对低分化鼻咽癌CNE2干细胞增殖、放疗敏感性的影响

目的探讨蛇床子素对低分化鼻咽癌CNE2干细胞增殖、放疗敏感性的影响及其机制。方法采用无血清培养基分离培养低分化鼻咽癌CNE2细胞的干细胞;流式细胞仪检测干细胞表面标记物CD44+/CD24-low的表达和乙醛脱氢酶(ALDH)活性;MTT检测不同质量浓度(0、20、40、80μg/m L)蛇床子素处理后,CNE2干细胞增殖能力的差异;克隆形成实验检测蛇床子素(40μg/m L)联合放疗后(0、2、5 Gy),CNE2干细胞克隆形成能力的差异;Western blotting法检测不同质量浓度蛇床子素处理、蛇床子素联合不同放射剂量放疗后,鼻咽癌CNE2干细胞中p-GSK-3β、β-catenin、Cyclin D1蛋白的表达水平。结果在无血清培养基中可分离培养稳定传代的低分化鼻咽癌CNE2干性细胞。细胞CD44+/CD24-low、ALDH+的表达高于亲本细胞(P0.05);MTT结果显示,与对照组相比,不同质量浓度的蛇床子素作用不同时间后,干细胞增殖抑制率明显增加(P0.05),且随着蛇床子素质量浓度的增加及作用时间的延长,其抑制作用增强(P0.05);克隆形成实验结果显示,与对照组相比,各给药组干细胞克隆形成率均明显降低,蛇床子素+放疗组显著低于蛇床子素组及放疗组(P0.05);Western blotting检测结果显示,随着蛇床子素质量浓度的增加,放射剂量的增加,与对照组相比,干细胞p-GSK-3β、β-catenin、Cyclin D1的蛋白表达水平均明显降低,蛇床子素+放疗组显著低于蛇床子素组及放疗组(P0.05);结论蛇床子素能有效抑制低分化鼻咽癌CNE2干细胞的增殖并促进其放疗敏感性,其机制可能是蛇床子素抑制肿瘤干细胞p-GSK-3、β-catenin、Cyclin D1蛋白的表达,从而抑制了干细胞增殖,促进了放疗敏感性。     

蛇床子素抗癌作用及其剂型研究进展

蛇床子素是伞形科植物蛇床子的主要活性成分,许多临床和现代药理实验研究表明,蛇床子素具有抗高血压,抗心律失常,抗肿瘤,抗诱变以及减缓神经退行性疾病进展的功效。另外蛇床子素对多种癌症均具有一定的抵抗作用,如：神经胶质癌、乳腺癌、胰腺癌、肺癌、胃癌等。然而蛇床子素作为一种香豆素类化合物,具有口服吸收差,生物利用度低等缺点,为改善其缺点,需要制备蛇床子素的新剂型,如,脂质体、胶束、固体分散体等,以获得更好的临床效果。该文归纳总结了近几年来蛇床子素治疗癌症的药理作用及其剂型研究,希望能为以后的研究提供帮助。